Mass spectrometry from surfaces

ABSTRACT

A Time-Of-Flight mass spectrometer ( 1 ) is configured with a pulsing region ( 10 ) and electronic controls to cause the directing of ions to a surface ( 12 ) in the Time-Of-Flight pulsing region ( 10 ). The population of ions resulting from the collecting of said ions on or near said surface ( 12 ) is subsequently accelerated into the Time-Of-Flight tube ( 17 ) for mass to charge analysis. Ions produced away from said surface ( 12 ) can be directed to the surface ( 12 ) with high or low surface collisional energies. Higher energy ion collisions with the surface ( 12 ) can result in Surface Induced Dissociation fragmentation and the resulting ion fragment population can be mass analyzed. Mass analysis can be performed prior to directing the ions to the surface allowing MS/MS Time-Of-Flight mass analysis with SID. Ion to surface low energy collisions or soft landings resulting in little or no ion fragmentation provide a means for spatially focusing ions on or near the surface prior to accelerating the surface collected ions into the Time-Of-Flight tube.

This application claims benefit of provisional application 60/072,246filed Jan. 23, 1998.

FIELD OF THE INVENTION

The present invention relates to the field of mass spectrometry and inparticular to apparatus and methods for ion-surface interactions withinmass analyzers.

BACKGROUND OF THE INVENTION

Mass spectrometers are used to analyze sample substances (containingelements or compounds or mixtures of elements or compounds) by measuringthe mass to charge of ions produced from a sample substance in an ionsource. A number of types of ion sources that can produce ions fromsolid, liquid or gaseous sample substrates have been combined with massspectrometers. Ions can be produced in vacuum using ion sources,including, but not limited to, Electron Ionization (EI), ChemicalIonization (CI, Laser Desorption LD), Matrix Assisted Laser Desorption(MALDI), Fast Atom Bombardment (FAB), Field Desorption (FD) or SecondaryIon Mass Spectrometry (SIMS). Alternatively, ions can be produced at ornear atmospheric pressure using ion sources, including, but not limitedto, Electrospray (ES), Atmospheric Pressure Chemical Ionization (APCI)or Inductively Coupled Plasma (ICP). Ion sources that operate atintermediate vacuum pressures such as Glow Discharge Ion Sources havealso been used to generate ions for mass spectrometric analysis. Ionsources that operate in vacuum are generally located in the vacuumregion of the mass spectrometer near the entrance to the mass analyzerto improve the efficiency of ion transfer to the detector. Ion sourcesthat produce ions in vacuum have also been located outside the regionnear the mass spectrometer entrance. The ions produced in a locationremoved from the mass analyzer entrance must be delivered to theentrance region of the mass spectrometer prior to mass analysis.Atmospheric or intermediate pressure ion sources are configured todeliver ions produced at higher pressure into the vacuum region of themass analyzer. The geometry and performance of the ion optics used totransport ions from an ion source into the entrance region of a givenmass analyzer type can greatly affect the mass analyzer performance.This is particularly the case with Time-Of-Flight mass analyzers, inwhich the initial spatial and energy distribution of the ions pulsedinto the flight tube of a Time-Of-Flight mass analyzer affects theresulting mass to charge analysis resolution and mass accuracy.

Mass analysis conducted in a Time-Of-Flight mass (TOF) spectrometer isachieved by accelerating or pulsing a group of ions into a flight tubeunder vacuum conditions. During the flight time, ions of different massto charge values spatially separate prior to impacting on a detectorsurface. Ions are accelerated from a first acceleration or pulsingregion and may be subject to one or more acceleration and decelerationregions during the ion flight time prior to impinging on a detectorsurface. Multiple ion accelerating and decelerating stages configured inTime-Of-Flight mass spectrometers aid in compensating or correcting forthe initial ion spatial and energy dispersion of the initial ionpopulation in the first ion pulsing or accelerating region. The mostcommon lens geometry used in the first TOF ion pulsing or acceleratingregion is two parallel planar electrodes with the electrode surfacesoriented perpendicular to the direction of ion acceleration into theTime-Of-Flight tube. The direction of the initial ion acceleration isgenerally in a direction parallel with the TOF tube axis. A linearuniform electric field is formed in the gap between the two parallelplanar electrodes when different electrical potentials are applied tothe two electrodes. The planar electrode positioned in the direction ofion acceleration into the TOF tube is generally configured as a highlytransparent grid to allow ions to pass through with minimal interferenceto the ion trajectories. To maximize the performance of a Time-Of-Flightmass analyzer, it is desirable to initiate the acceleration of ions inthe pulsing region with all ions initially positioned in a planeparallel with the planar electrodes and initially having the sameinitial kinetic energy component in the direction of acceleration.Consequently, when ions are generated in or transported into the initialaccelerating or pulsing region of a Time-Of-Flight mass analyzer,conditions are avoided which lead to ion energy or spatial dispersion atthe initiation of ion acceleration into the Time-Of-Flight tube driftregion. As a practical matter, a population of gaseous phase ionslocated in the pulsing region will have a non-zero spatial and kineticdistribution prior to pulsing into a Time-Of-Flight tube drift region.This non zero spatial and kinetic energy spread may degradeTime-Of-Flight mass to charge analysis resolution, sensitivity and massmeasurement accuracy. In one aspect of the present invention, thespatial and energy spread of an ion population is minimized prior toaccelerating the population of ions into a Time-Of-Flight tube driftregion.

When ion spatial and energy spread can not be avoided in the TOF pulsingor first accelerating region, it is desirable to have the ion energy andspatial distributions correlated so that both can be compensated andcorrected for during the ion flight time prior to hitting the detector.A correlation between the ion kinetic energy component in the TOF axialdirection and spatial spread can occur in the TOF pulsing region whenspatially dispersed ions with a non random TOF axial kinetic energycomponent are accelerated in a uniform electric field formed between twoparallel electrodes. Wiley et. al., The Review of Scientific Instruments26(12):1150-1157 (1955) described the configuration and operation of asecond ion accelerating region to refocus ions of like mass to chargealong the TOF flight path that start their acceleration with acorrelated spatial and energy spread. Electrode geometries in the TOFtube and voltages applied to these electrodes can be varied with thistechnique to position the focal plane of a packet of ions of the samemass to charge value at the detector surface to achieve maximumresolution. The Wiley-McClaren focusing technique improves resolutionwhen ions occupying a finite volume between two parallel plateelectrodes are accelerated. In a uniform electric accelerating field,ions of the same m/z value located closer to the repelling electrodewill begin their acceleration at a higher potential than an ion of thesame m/z initiating its acceleration at a position further from therepelling electrode. The ion that starts its acceleration nearer to therepelling electrode surface at a higher potential, must travel furtherthan the slower ion which starts its acceleration at a lower potentialcloser to the extraction grid or electrode. At some point in thesubsequent ion flight, the faster ion will pass the slower ion of thesame m/z value. By adding a second accelerating region, the location ofthe point where the ions having the same mass to charge value pass andhence are “focused” in a plane, can be optimized to accommodate adesired flight time and flight tube geometry. The focal point occurringin the first field free region in the TOF drift tube can be “reflected”into a second field free region using an ion mirror or reflector in theion flight path.

Variations in ion flight time can also be caused by initial ion velocitycomponents not correlated to the spatial spread. This non-correlated ionkinetic energy distribution can be compensated for, to some degree, bythe addition of an ion reflector or mirror in the ion flight path. Ionsof the same m/z value with higher kinetic energy in the TOF axialdirection will penetrate deeper into the decelerating field of an ionreflector prior to being re-accelerated in the direction of thedetector. The ion with higher kinetic energy experiences a longer flightpath when compared to a lower energy ion of the same m/z value.Subjecting an ion to multiple accelerating and decelerating electricfields allows operation of a TOF mass analyzer with higher orderfocusing to improve resolution and mass accuracy measurement.Configuration and operation of an Atmospheric Pressure Ion SourceTime-Of-Flight mass analyzer with higher order focusing is described byDresch in U.S. patent application Ser. No. 60/021,184. Higher orderfocusing corrections can not entirely compensate for initial ion kineticenergy spread in the TOF axial direction that is not correlated with ionspatial spread in the initial pulsing or ion acceleration region. Also,higher order focusing can not entirely compensate for ion energy orspatial spreads which occur during ion acceleration, deceleration orfield free flight due to ion fragmentation or ion collisions withneutral background molecules. A ion kinetic energy distribution notcorrelated to the ion spatial distribution can occur when ionizationtechniques such as MALDI are used. In MALDI ionization, thesample-bearing surface is located in the initial acceleration region ofa Time-Of-Flight mass spectrometer. A laser pulse impinging on a samplesurface, in a MALDI ion source, creates a burst of neutral molecules aswell as ions in the initial accelerating region of a Time-Of-Flight massanalyzer. Ion to neutral molecule collisions can occur during ionextraction and acceleration into the TOF drift tube resulting in an ionkinetic energy spread, ion fragmentation, degradation of resolution anderrors in mass to charge measurement. This problem increases ifstructural information via ion fragmentation is desired using MALDITime-Of-Flight mass analysis. Higher energy laser pulses used in MALDIto increase the ion fragmentation also result in increased neutralmolecule ablation from the target surface. Even in the absence ofion-neutral collisions, ions generated from the target surface have aninitial velocity or kinetic energy distribution that is not wellcorrelated to spatial distribution in the first ion acceleration region.This initial non-correlated kinetic distribution of the MALDI generatedion population can degrade resolution, and mass accuracy performance inTime-Of-Flight mass analysis.

A technique, termed delayed extraction, has been developed where theapplication of an electric field to accelerate ions into the TOP drifttube is delayed after the MALDI laser pulse is fired to allow time forthe neutral gas to expand, increasing the mean free path prior to ionacceleration. By applying a small reverse accelerating field during theMALDI laser pulse and delaying the acceleration of ions into theTime-Of-Flight tube drift region, as described by Vestal et. al. in U.S.Pat. No. 5, 625,184, some portion of the low m/z ions can be eliminated.A portion of the low m/z ions, primarily matrix related ions, created inthe MALDI process are accelerated back to the sample surface andneutralized when the reverse electric field is applied. A portion of theslower moving higher mass to charge ions do not return to the targetsurface as rapidly as the lower molecular weight ions when the reverseaccelerating field is applied. After an appropriate delay, these highermolecular weight ions may be forward accelerated into the TOP tube driftregion by switching the electric field applied between the twoelectrodes in the first ion acceleration region. Delayed extraction alsoallows many of the fast fragmentation processes to occur prior toaccelerating ions into the Time-Of-Flight tube drift region, resultingin improved mass to charge resolution and mass accuracy measurements forthe ions produced in fast fragmentation processes. The delayedextraction technique reduces the ion energy deficit which can occur dueto ion-neutral collisions in the first accelerating region but does notentirely eliminate it, particularly with higher energy laser pulses.Also, delayed extraction is effective in improving MALDI Time-Of-Flightperformance when lasers with longer pulse durations are used. However,even with delayed extraction, there is a limit to the length of delaytime, the magnitude of the reverse field during the delay period, thelaser power used and the duration of a laser pulse before overallsensitivity or Time-Of-Flight performance is degraded. The delayedextraction technique requires a balancing of several variables toachieve optimal performance, often with compromises to theTime-Of-Flight mass analysis performance over all or some portion of themass to charge spectrum generated. The present invention improves theperformance of MALDI Time-Of-Flight without imposing the restrictions orlimitations of delayed extraction techniques and provides more uniformTime-Of-Flight mass analysis performance over a wider mass to chargerange.

When ions are generated in an ion source positioned external to theTime-Of-Flight pulsing or first acceleration region, a technique termed“orthogonal” pulsing has been used to minimize effects of the kineticenergy distribution of the initial ion beam. This orthogonal pulsingtechnique first reported by The Bendix Corporation Research LaboratoriesDivision, Technical Documentary Report No. ASD-TDR-62-644, Part 1, April1964, has become a preferred technique to interface external ionsources, particularly Atmospheric Pressure Ionization Sources, withTime-Of-Flight mass analyzers. The ion beam produced from an AtmosphericPressure Ion Source (API) or an ion source that operates in vacuum, isdirected into the gap between the two parallel planar electrodesdefining the first accelerating region of the TOF mass analyzer. Theprimary ion beam trajectory is directed to traverse the gap between thetwo parallel planar electrodes in the TOF first accelerating regionsubstantially orthogonal to axis of the direction of ion accelerationinto Time-Of-Flight tube. With the orthogonal pulsing technique, anykinetic energy distribution in the primary ion beam is not coupled tothe ion velocity component oriented in the direction of ion accelerationinto the Time-Of-Flight tube drift region. The primary ion beam kineticenergy spread oriented along the beam axis only affects the location ofion impact on the planar detector surface, not the ion arrival time atthe detector surface. Apparatus and methods have been developed toimprove the duty cycle TOF mass analyzers configured with linear ororthogonal pulsing geometries.

Dresch et. al. in U.S. Pat. No. 5,689,111 describe an apparatus andmethod for improving the duty cycle and consequently the sensitivity ofa Time-Of-Flight mass analyzer. Ions contained in a continuous ion beamdelivered from an atmospheric pressure ion source into a multipole ionguide, are trapped in the multipole ion guide and selectively releasedfrom the ion guide exit into the TOF pulsing region. This apparatus andtechnique delivers ion packets into the pulsing or first accelerationregion of a TOF mass analyzer from a continuous ion beam with higherefficiency and less ion loss than can be achieved with a continuousprimary ion beam delivered directly into the TOF pulsing region. Iontrapping of a continuous ion beam in an ion guide effectively integratesions delivered in the primary ion beam between TOF pulses. When thisapparatus and technique is applied to an orthogonal pulsing TOFgeometry, portions of the mass to charge range can be prevented frombeing accelerated into the Time-Of-Flight drift region, reducingunnecessary detector channel dead time, resulting in improvedsensitivity and dynamic range. Operation with the orthogonal pulsingtechnique has provided significant Time-Of-Flight mass analysisperformance improvements when compared with the performance usingin-line ion beam pulsing techniques. Even with orthogonal pulsing, it isnot always possible to achieve optimal primary ion beam characteristicsin the pulsing region whereby all orthogonal velocity components areeliminated or spatially correlated. One embodiment of the inventioncombines orthogonal ion beam introduction into the TOF pulsing regionwith ion collection on a surface prior to pulsing the surface collectedion population into the TOF tube drift region. The spatial and energycompression of the ion population on the collecting surface prior topulsing into the TOF tube drift region improves the Time-Of-Flightperformance and analytical capability.

The orthogonal pulsing technique has been configured in hybrid or tandemmass spectrometers that include Time-Of-Flight mass analysis. Two ormore individual mass analyzers are combined in tandem or hybrid TOF massanalyzers to achieve single or multiple mass to charge selection andfragmentation steps followed by mass analysis of the product ions.Identification and/or structural determination of compounds is enhancedby the ability to perform MS/MS or multiple MS/MS steps (MS/MS^(n)) in agiven chemical analysis. It is desirable to control the ionfragmentation process so that the required degree of fragmentation for aselected ion species can be achieved in a reproducible manner.Time-Of-flight mass analyzers have been configured with magnetic sector,quadrupole, ion trap and additional Time-Of-Flight mass analyzers toperform mass selection and fragmentation prior to a final Time-Of-Flightmass analysis step. Gas phase Collisional Induced Dissociation (CID) andSurface Induced Dissociation (SID) techniques have been used toselectively fragment gas phase ions prior to TOF mass analysis orcoupled to the ion flight path in the Time-Of-Flight tube. CID ionfragmentation has been the most widely used of the two techniques.Magnetic sector mass analyzers have been configured to perform mass tocharge selection with higher energy CID fragmentation of mass to chargeselected ions to aid in determining the structure of compounds. Lowerenergy CID fragmentation achievable in quadrupoles, ion traps andFourier Transform mass analyzers, although useful in many analyticalapplications, may not provide sufficient energy to effectively fragmentall ions of interest. High energy CID fragmentation can yield side chaincleavage fragment ion types known as w type fragments. This type offragmentation is less common in low energy CID processes. The additionalion fragmentation information achievable with higher energyfragmentation techniques can be useful when determining the molecularstructure of a compound.

An alternative to CID ion fragramentation is the use of Surface InducedDissociation to fragment ions of interest. The capability of the SurfaceInduced Dissociation ion fragmentation technique has been reported for anumber of mass analysis applications. Wysocki et. al. J. Am. Soc. forMass Spectrom, 1992, 3, 27-32 and McCormack et. al., Anal. Chem. 1993,65, 2859-2872, have demonstrated the use of SID ion fragmentation withquadrupole mass analysis to controllably and reproducibly achieveanalytically useful fragmentation information. McCormack et. al. showedthat with collisional energies below 100 eV, w and d type ion fragmentscan be produced from some peptides. Kiloelectronvolt gas phasecollisions may be required to achieve similar ion fragmentation. Higherinternal energy transfer to an ion can be achieved in SID than with gasphase CID processes allowing the possibility of fragmenting large ions,even those with a large number of degrees of freedom and low numbers ofcharges. Also, the ion collisional energy distributions can be moretightly controlled with SID when compared with gas phase CID processes.A variety of collision surfaces have been used in SID experimentsranging from metal conductive surfaces such as copper and stainlesssteel to self-assembled aklyl-monolayer surfaces surfaces such asoctadecanethiolate (CH3(CH2) 17SAu), ferrocence terminated selfassembled aklyl-monolayer surfaces and fluorinated self-assembledmonolayer (F-SAM) surfaces (CF3(CF2)7(CH2)2 SAu). The self-assembledmonolayer surfaces tend to reduce the charge loss to the surface duringthe SID process. Winger et. al. Rev. Sci. Instrum., Vol 63, No. 12, 1992have reported SID studies using a magnetic sector-dual electricsector-quadrupole (BEEQ) hybrid instrument. They showed kinetic energydistributions of up to +/−3 eV for parent and fragment ions leaving aperdeuterated alkyl-monolayer surface after a 25 eV collision. SIDcollisions have been performed by impacting ions traversing aTime-OF-Flight flight tube onto surfaces positioned in the flight tubeand Time-OF-Flight mass to charge analyzing the resulting ionpopulation. Some degree of mass to charge selection prior to SIDfragmentation has been achieved by timing the deflection of ions as theinitial pulsed ion packet traverses the flight tube. SID surfaces havebeen positioned in the field free regions and at the bottom of ionreflector lens assemblies in TOF mass analyzers. The resulting TOF massspectra of the SID fragment ions in these instruments generally have lowresolution and low mass measurement accuracy due in part to the broadenergy distributions of the SID fragment ions leaving the surface. Apopulation of ions acquiring a kinetic energy spread during its flightpath or during a re-acceleration step in an ion reflector degrades TOFperformance. The present invention reduces the broad kinetic energydistributions of ions produced by SID fragmentation prior to conductingTime-Of-Flight mass analysis. In the present invention, one or moresteps of ion mass to charge selection and CID fragmentation can beconducted prior to performing a SID fragmentation step in the TOFpulsing region.

The present invention relates to the configuration and operation of aTime-Of-Flight mass analyzer in a manner that results in improved TOFperformance and range of TOF analytical capability. Ions produced froman ion source are directed to a surface located in the pulsing or firstacceleration region of a Time-Of-Flight mass analyzer prior toaccelerating the ions located on or near the surface into theTime-Of-Flight tube drift region. Depending on the energy at which theions are brought to the surface and the surface composition, surfaceinduced dissociation or ion to surface reactions may or may not occur.With low energy or soft-landing conditions, surface induced dissociationmay be avoided and the surface serves to reduce the ion kinetic energydistribution and spatial spread in the TOF tube axial direction prior toaccelerating the surface collected ions into the Time-Of-Flight tubedrift region. The soft landing surface collection or surface “focusing”of ions improves the resolution and duty cycle in Time-Of-Flight massanalysis. Ions entering the TOF first accelerating region are directedonto a surface by applying a reverse potential between the collectingsurface and the opposing electrode. Ions collected on the surface areextracted from the surface and or accelerated into the flight tube of aTime-Of-Flight mass analyzer by reversing the electric field between theion collecting surface and the opposing or extracting electrode or grid.The surface collection and forward acceleration of ion packets can occurat repetition rates exceeding 20 kilohertz allowing TOF pulse repetitionrates typically used in gas phase orthogonal pulsing TOF. A low energylaser pulse can be used to release collected ions from surfaces in thepresence of an accelerating field. It is desirable to avoid damaging thesurface substrate when extracting ions from the surface to reduceunwanted chemical noise in the resulting mass spectra. Frey et. al.,Science, 275, 1450, 1997 and Luo et. al., Proceedings of the 45th ASMSConference on Mass Spectrometry and Allied Topics, 819, 1997 havestudied the modification of surface chemistries in F-SAM surfaces. Theauthors reported using soft-landing of ions on F-SAM surfaces, and aftersome delay, followed by sputtering of the surface with Xe+ whileconducting mass spectrometric analysis. Surface analysis of soft-landedF-SAM surfaces was also conducted using 15-keV Ga+ ion sputtering withTOF mass analysis. Unfortunately, sputtering of ions or neutralmolecules damages the surface substrate producing surface substraterelated ions. The authors have reported thermally desorbing orevaporating the products of EI generated ions using temperatures rangingfrom 300° to 400° C. Thermally desorbed ions were mass to chargeanalyzed with a quadrupole mass spectrometer. Apparatus and methodsconfigured according to the invention can be used achieve ion extractionfrom a surface after a surface collection step followed by TOF mass tocharge analysis without ion sputtering. Depending on the collectingsurface material configured, however, some surface damage may besustained by the sample ions impacted the surface during a surfaceinduced dissociation fragmentation step.

The magnitude of the reverse electrical potential applied between thesurface and the extraction electrode determines the impact energy an ionwill have on the surface prior to being forward accelerated into theTime-Of-Flight tube drift region. Ions can be directed to the collectingsurface with a soft-landing by applying a low electrical field betweenthe collecting surface and the counter electrode in the TOF pulsingregion. Surface induced dissociation of ions can be achieved, prior topulsing the resulting ion population into the Time-Of-Flight driftregion, by increasing the reverse electric field directing the ions tothe collecting surface. A variety of ion sources can be configuredaccording to the invention with ability to conduct SID with TOF massanalysis. Ions can be produced directly in the TOF first accelerationregion or produced external to the first acceleration region. Atime-of-flight configured according to the invention can be selectivelyoperated with or without surface collection, surface induceddissociation or reaction of ions with surfaces prior to Time-Of-Flightmass analysis. The invention retains the ability to conduct existingionization and TOF analysis techniques. The added ion surface collectionand SID fragmentation capability greatly expands the overall analyticalrange of a Time-Of-Flight mass analyzer. A Time-Of-Flight mass analyzerconfigured and operated according to the invention can be included in ahybrid mass analyzer enhancing MS/MS or MS/MS^(n) operation and operatedwith a range of ion sources.

SUMMARY OF THE INVENTION

The pulsing or ion extraction region of a Time-Of-Flight massspectrometer configured with two parallel planar electrodes isconfigured such that neutral, retarding and ion extraction electricfields can be applied between the two electrodes. The electronicsproviding voltage to these electrodes is configured such that theneutral, forward and reversed biased electric fields can be rapidlyapplied by switching between power supplies. In one embodiment of theinvention, ions produced in an ion source form an ion beam that entersthe pulsing region with the ion beam trajectory substantially parallelto the surfaces of the planar electrodes that define the pulsing region.During the time period when ions are entering the TOT pulsing region, aslight reverse bias field is applied across the two planar electrodes todirect the ions to the collecting electrode surface. In this manner ionsare collected on or near the electrode surface for a selected period oftime before a forward bias electric field between the planar electrodesis applied, accelerating ions from the ion collecting surface into theTOF tube drift region of the mass analyzer. The primary ion beam isprevented from entering the pulsing region just prior to applying theion forward accelerating potential to eliminate any ions located in thegap between the electrodes prior to ion acceleration into the TOF tube.The soft-landing continuous collecting of ions on or near the collectingelectrode surface, reduces the initial ion beam spatial and energyspread of the primary ion beam prior to acceleration or pulsing of theion population into the Time-Of-flight tube drift region. Acceleratingan ion packet initially shaped as a thin plane at or near the collectingsurface into the TOF flight tube improves the resolution and massaccuracy compared with an orthogonally pulsed gas phase primary ionbeam. The duty cycle is improved by collecting all m/z value ions withequal efficiency prior to pulsing. The duty cycle of conventionalnon-trapping continuous beam orthogonal pulsing decreases with the ionmass to charge value. Collecting ions on a surface prior to pulsingreduces the mass to charge duty cycle discrimination in conventionalcontinuous ion beam orthogonal pulsing Time-Of-Flight mass analysis. Theduty cycle is also improved because the process of collecting ions onthe collecting electrode surface prior to pulsing, serves as a means ofintegrating ions prior to acceleration into the TOF tube. The ionintegration or collection time, however, is limited by space chargebuildup on the dielectric or non-conducting collecting surfacepotentially limiting the number of ions which may be effectivelycollected prior to pulsing. The space charging at the collecting surfacecan be controlled to some degree by varying the pulse repetition rate ofions into the TOF mass analyzer. Pulse rates exceeding 20 KHz can beused limited only by the flight time of the mass to charge range ofinterest.

In another embodiment of the invention, the Time-Of-Flight pulsingregion configured for orthogonal pulsing, comprises two parallel planarelectrodes, between which neutral, retarding and accelerating fields maybe applied. The electric fields can be applied by rapidly switchingpower supply outputs to one or both electrodes. Ions traveling into thepulsing region with trajectories substantially parallel to the planarelectrode surfaces, traverse the pulsing region with a neutral electricfield applied between the two planar electrodes. After a selected periodof time, a retarding or reverse electric field is applied between theplanar electrodes directing the ions located in the pulsing region gaptoward the collecting electrode surface. After a preset delay, anaccelerating field is applied between the two planar electrodes and theions are accelerated from the collecting electrode surface into theTime-Of-Flight drift region. One or more ion surface collecting pulsescan precede an extraction pulse into the Time-Of-Flight drift region.The magnitude of the reverse or collecting electric field can be set tocause surface induced dissociation (SID) or, alternatively, soft landingof ions when they impact on the surface prior to accelerating theresulting parent or fragment ion population into the Time-Of-Flightdrift region.

In another embodiment of the invention, the collecting surface materialis configured to minimize charge exchange when an ion impacts thesurface. The ion collection time prior to extraction can be set to besufficiently long to create a space charge near the collecting surfaceas ions accumulate on or near the surface. This space charge aids inreleasing later arriving ions when a rapid reversal of the electricfield in the TOF first acceleration region is applied. Alternatively, alaser pulse can be applied to the surface to release ions from thesurface in the presence of an accelerating field or with delayedextraction conditions. The laser energy can be set so that sufficientenergy is available to release the existing ion population from thesurface while minimizing damage to the surface. In some applications,the collecting surface can be heated to facilitate the release of ionsfrom the surface. Collecting surface materials that minimize chargeexchange improve ion yield in SID or soft-landing operation resulting inhigher TOF sensitivity. The collecting electrode assembly can becomprised of multiple electrode segments with different voltages appliedto each segment. Voltages can be applied to a multiple segment electrodeduring ion collection to direct ions to a particular region of the totalelectrode surface or to contain ions in a potential well near adielectric surface as space charge occurs.

In yet another embodiment of the invention, ions are created in thepulsing region of a Time-Of-Flight mass analyzer while maintaining asubstantially neutral field between the two electrodes of the pulsingregion. The resulting ion population is subsequently directed to thecollecting electrode surface prior to pulsing of the ions into theTime-Of-Flight drift region. A specific example of such an embodiment ofthe invention is the configuration of an Electron Ionization (EI) sourcein the pulsing region of the Time-Of-Flight mass analyzer. Samplebearing gas is introduced at low pressure into the pulsing region of aTime-Of-Flight mass analyzer with a neutral electric field appliedacross the pulsing region gap. An electron-emitting filament is turnedon with the emitted electrons accelerated into the pulsing region gap toionize the gas phase sample present. The electron-emitting filament isturned off and a reverse electric field is applied across the pulsingregion gap to direct the gaseous ions produced to move toward thecollection electrode surface. When the EI generated ions have beencollected on or near the collecting electrode surface, an acceleratingfield is applied across the pulsing region gap to accelerate the ions ator near the collecting surface into the drift region of theTime-Of-Flight mass analyzer. The EI generated ions can be directed tothe collecting electrode surface with sufficient energy to cause surfaceinduced dissociation or with low energy to allow a non fragmentingsoft-landing. The sample gas may be supplied from a variety of inletsystems including but not limited to a gas chromatograph. Collecting EIgenerated ions on a surface prior to pulsing into the Time-Of-Flightdrift region reduces the ion kinetic energy distribution and spatialspread. This results in higher resolution and mass accuracyTime-Of-Flight mass to charge analysis. If electron ionization occurs inthe presence of a low amplitude surface collecting field, the ratio ofionization time to TOF ion acceleration and flight time can be increasedresulting in higher overall Time-Of-Flight duty cycle.

In another embodiment of the invention, the pulsing region of aTime-Of-Flight mass analyzer is comprised of two planar electrodespositioned substantially parallel and set a distance apart so as tocreate a gap between them. This gap is referred to as the TOF firstaccelerating or pulsing region. The first electrode positioned furthestfrom the Time-Of-Flight drift region is configured as an ion collectingsurface to which ions are directed prior to pulsing into theTime-Of-Flight drift region. A neutral, collecting or extractionelectric field can be applied between the two pulsing region electrodesto allow collecting of ions on or near the collecting electrode surfaceprior to pulsing the spatially compressed ions into the Time-Of-Flighttube drift region. Alternatively, a laser pulse can be applied to thecollecting surface to release ions rapidly into an accelerating ordelayed extraction field. In this embodiment of the invention, ionsgenerated external to the TOF pulsing region enter the pulsing region ina direction substantially not parallel to the planar electrode surfaceswhich bound the pulsing region. During the collection period, a reverseelectric field is applied across the pulsing region gap to direct ionsto the collecting electrode surface. The ions may enter the pulsingregion gap with an initial trajectory that is directed either toward oraway from the collecting surface. After the ion collection period, theelectric field is reversed in the pulsing region and ions on or near thecollecting surface are accelerated into the Time-Of-Flight tube for massto charge analysis. This embodiment of the invention, provides a meansfor directing ions into a Time-Of-Flight pulsing region from widevariety of ion sources or hybrid instrument electrode geometries withminimal impact on the Time-Of-Flight performance. Depending on theelectric field strength applied to direct ions to the collectingsurface, ions can impact the collecting surface with a soft-landing orwith sufficient energy to cause surface induced dissociationfragmentation. Ions can be collected for a period of time prior topulsing into the Time-Of-Flight drift region, improving the duty cyclefor some applications and operating modes.

In another embodiment of the invention, non-planar electrodes may beconfigured in the pulsing region. Alternatively, the pulsing or firstaccelerating region of the time-of-flight mass analyzer may beconfigured with a three dimensional quadrupole ion trap or a multipoleion guide. One or more surfaces within these non-planar electrodegeometries may be configured to serve as a collecting surface orsurfaces to reduce the ion population spatial and energy distributionprior to accelerating the ion population into the Time-Of-Flight massanalyzer. Conversely, the non-planar surfaces may be used to fragmentions by SID prior to accelerating the resulting ion population into aTOF tube. When three dimensional quadrupole ion traps or multipole ionguides are configured in the TOF pulsing region, ions released from thesurfaces in these electrode geometries may be trapped by the RF electricfields applied to the electrodes prior to extracting the ions into theTime-Of-Flight tube. The gas phase RF trapping of ions after surface ioncollection or SID fragmentation is an added step in a TOF mass analysissequence when compared to the planar electrode geometry configured inthe pulsing region. The ion trapping, however, may be used to enhancethe analytical capability of the Time-Of-Flight mass analyzer. The sameanalytical sequences described for planar geometry electrodes configuredin the TOF pulsing region can be applied to the non-planar pulsingregion electrode configurations to improve Time-Of-Flight performanceand analytical capability.

The invention can be configured with a wide range of ion sourcesincluding but not limited to, Electron Ionization (EI), ChemicalIonization (CI), Laser Desorption (LD), Matrix Assisted Laser Desorption(MALDI), Electrospray (ES), Atmospheric Pressure Chemical Ionization(APCI), Pyrolysis MS, Inductively Coupled Plasma (ICP), Fast AtomBombardment (FAB), and Secondary Ion Mass Spectrometry (SIMS). Ions maybe subjected to one or more mass to charge selection and/orfragmentation steps prior to entering the Time-Of-Flight pulsing region.The Time-Of-Flight mass analyzer may be configured as a single mass tocharge analyzer or as part of a hybrid or tandem instrument. A hybridTime-Of-Flight mass analyzer configured according to the invention, mayinclude multipole ion guides including quadrupole mass analyzers,magnetic sector, ion trap or additional Time-Of-Flight mass analyzers.According to the invention, analytical sequences can be run that includeion surface induced dissociation alternating with or sequential to gasphase collision induced dissociation in hybrid or tandem mass analyzerconfigurations. The invention can be used to study ion-surfaceinteractions as well with prior mass to charge selected ion populations.The collecting surface described in the invention may be comprised of avariety of materials including but not limited to metals or otherconductor material, semiconductor materials, dielectric materials, SelfAssembled Monolayers (SAM) or combinations of materials.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a diagram of an orthogonal pulsing Time-Of-Flight massanalyzer configured with an Electrospray ion source and an ioncollecting surface in the Time-Of-Flight pulsing region.

FIGS. 2A through 2D diagram of one embodiment of the invention whereininitially trapped ions are introduced batchwise into the Time-Of-Flightpulsing region, collected on the pulsing region collecting surface andsubsequently accelerated into the Time-Of-Flight tube.

FIGS. 3A through 3D diagram one embodiment of the invention wherein ionsare collected on the collecting surface in the Time-Of-Flight pulsingregion from a continuous ion beam prior to acceleration into theTime-Of-Flight tube.

FIG. 4 is a diagram of one embodiment of the invention wherein multiplepower supplies are switched to electrostatic lenses to allow surfacecollection of ions in a TOF pulsing region and acceleration of said ionsfrom the pulsing region of a Time-Of-Flight mass analyzer.

FIG. 5A is a top view diagram of one embodiment of a dielectriccollecting surface electrically insulated from a surrounding electrode.

FIG. 5B is a side view diagram of a multilayer dielectric collectingsurface with power supplies, switches and control electronics.

FIG. 6 is a diagram of an embodiment of a collecting surface of piezoelectric material electrically insulated from a surrounding electrode.

FIGS. 7A through 7D diagram one embodiment of the invention wherein,ions produced by Matrix Assisted Laser Desorption Ionization external tothe pulsing region of a time-of-flight mass analyzer are collected on asurface in the pulsing region prior to accelerating the ions into theflight tube of a Time-Of-Flight mass analyzer.

FIG. 8 is a diagram of one embodiment of the invention wherein, ions areproduced from a position above the collecting surface of aTime-Of-Flight mass analyzer.

FIG. 9 is a diagram of one embodiment of the invention wherein, ions areproduce from an initial position behind the collecting surface of atime-of-flight mass analyzer.

FIG. 10 is a diagram of one embodiment of the invention wherein, ionsproduced by MALDI ionization are directed through an orifice in thecollecting surface.

FIGS. 11A through 11D diagram one embodiment of the invention whereinions produced by electron ionization in the pulsing region of aTime-Of-Flight mass analyzer are collected on a surface prior toacceleration into the flight tube of a Time-Of-Flight mass analyzer.

DETAILED DESCRIPTION OF THE INVENTION AND THE PREFERRED EMBODIMENTS

Time-Of-Flight (TOF) mass analyzers that incorporate a linear or anorthogonal pulsing region as a means for pulsing ion bunches into theTime-Of-Flight tube are well known to those skilled in the art.Orthogonal pulsing Time-Of-Flight (O-TOF) mass analyzers are typicallyconfigured with the ion source located external to the TOF pulsingregion. The primary beam of ions exiting an ion source is directed intothe pulsing region of the TOF with a trajectory oriented substantiallyorthogonal to the axis of the Time-Of-Flight tube drift region. Severaltypes of ion sources can be interfaced with orthogonal pulsingTime-Of-Flight mass analyzers. These include but are not limited toElectron Ionization (EI), Chemical ionization (CI), Photon andMultiphoton Ionization, Fast Atom Bombardment (FAB), Laser Desorption(LD), Matrix Assisted Laser Desorption (MALDI). Thermospray (TS),sources as well as Atmospheric Pressure Ion (API) sources includingElectrospray (ES), Atmospheric Pressure Chemical Ionization (APCI),Pyrolysis and Inductively Coupled Plasma (ICP) sources. Othogonalpulsing Time-Of-Flight mass analyzers have been configured in tandem orhybrid mass spectrometers. Ions can be delivered to the Time-Of-Flightorthogonal pulsing region from several mass analyzer types including butnot limited to multipole ion guides including quadrupoles, hexapoles oroctopoles or combinations thereof, triple quadrupoles, magnetic sectormass analyzers, ion traps, Time-Of-Flight, or Fourier transform massanalyzers. Hybrid or tandem instruments allow one or more steps of massto charge selection or mass to charge selection with fragmentation (MSor MS/MS^(n)) combined with orthogonal pulsing Time-Of-Flight massanalysis.

One preferred embodiment of the invention is the configuration of anorthogonal Time-Of-Flight pulsing region such that ions entering thepuling region can be directed to a collecting surface electrode locatedin the pulsing region prior to pulsing the ions into the Time-Of-Flightdrift region. The energy by which ions are directed to the surface canbe varied by setting the appropriate voltages applied to the two planarelectrodes defining the TOF pulsing region. Ions can be directed to thecollecting surface electrode with low energy to allow soft-landingconditions with little or no fragmentation. Soft-landing collection ofions at the collection electrode surface prior to acceleration of theions into the Time-Of-Flight drift region serves to decrease the ionenergy distribution and spatial spread resulting in increasedTime-Of-Flight resolution and mass accuracy. Alternatively, ions can bedirected to the collecting electrode surface with energy sufficient tocause surface induced dissociation (SID) fragmentation when the ionsimpact the surface. Surface induced dissociation can serve as theprimary ion fragmentation method or can compliment ion fragmentationaccomplished with gas phase collisional induced dissociation conductedin a tandem MS or hybrid mass spectrometer prior to performingTime-Of-Flight mass analysis. One example of a hybrid mass analyzer witha preferred embodiment of the invention is diagrammed in FIG. 1.

FIG. 1 is a diagram of an orthogonal pulsing Time-Of-Flight massanalyzer configured with an Electrospray (ES) ionization source and amultipole ion guide ion trap. The multipole ion guide that extendscontinously into multiple vacuum pumping stages can be operated in RFonly, mass to charge selection or ion fragmentation mode as described inU.S. Pat. No. 5,652,427 and 5,689,111, and U.S. Pat. No. applicationswith Ser. Nos. 08/694,542 and 08/794,970. The instrument diagrammed canbe operated in MS or MS/MS^(n) mode with gas phase collisional induceddissociation (CID). In addition, the invention allows surface induceddissociation and surface collection of ions prior to ion pulsing intothe flight tube of the time-Of-Flight mass analyzer. HybridTime-Of-Flight mass analyzer 1 diagrammed in FIG. 1 includesElectrospray ion source 2, four vacuum pumping stages 3, 4, 5 and 6respectively, multipole ion guide 8 that extends into vacuum pumpingstages 4 and 5, orthogonal Time-Of-Flight pulsing region 10 withcollecting surface electrode 11 and removable collecting surface 12,Time-Of-Flight drift region 20, single stage ion reflector or mirror 21and detectors 22 and 23. Liquid sample bearing solution is sprayed intoElectrospray source 2 through needle 30 with or without pneumaticnebulization assist provided by nebulization gas 31. The resulting ionsproduced from the Electrospray ionization in Electrospray chamber 33 aredirected into capillary entrance orifice 34 of capillary 35. The ionsare swept though capillary 35 by the expanding neutral gas flow andenter the first vacuum stage 3 through capillary exit orifice 36. Aportion of the ions exiting capillary 35 continue through skimmerorifice 37 and enter multipole ion guide 8 at entrance end 40 located inthe second vacuum pumping stage 4. Ions exiting ion guide 8 pass throughorifice 43 in exit lens 41 and through orifice 44 of focusing lens 42and are directed into pulsing region or first accelerating region 10 ofTime-Of-Flight mass analyzer 45 with a trajectory that is substantiallyparallel to the surface of planar electrodes 11 and 13. The surfaces ofplanar electrodes 12 and 13 are positioned perpendicular to the axis ofTime-Of-Flight drift tube 20. Ion collecting surface 12 is configured aspart of collecting electrode 11 and counter or ion extraction electrode13 is configured with a high transparency grid through which ions areaccelerated into Time-Of-Flight drift region 20. The gap betweencollection electrode 11 with collection surface 12 and counter electrode13 defines the orthogonal pulsing or first accelerating region 10.

During orthogonal pulsing TOF operation, a substantially neutral or zeroelectric field is maintained in pulsing region 10 during the period whenions are entering the pulsing region from multipole ion guide 8. At theappropriate time, an accelerating field is applied between electrodes 11and 12 to accelerate ions into Time-Of-Flight tube drift region 20.During the initial ion acceleration and subsequent ion flight period,the appropriate voltages are applied to lenses 11, 13, 14, steeringlenses 15 and 16, flight tube 17, ion reflector electrodes 19, postaccelerating grid 18 and detector 23 to maximize Time-Of-Flightresolution and sensitivity. Ions pulsed from the Time-Of-Flight firstaccelerating region 10 may be directed to impact on detector 22 or 23depending on the analytical result desired. If the pulsed ion beam issteered with steering lenses 15 and 16, detector 22 or 23 can be tiltedas is described in U.S. Pat. No. 5,654,544 to achieve maximumresolution. TOF mass analyzer 1 may also be operated in orthogonalpulsing mode without collecting ions on surface 12 prior to pulsing intoTime-Of-Flight tube drift region 20. Prior to entering Time-Of-Flightpulsing region 10, the original ion population produced by Electrosprayionizaton may be subjected to one or more mass selection and/orfragmentation steps. Ions may be fragmented through gas phasecollisional induced dissociation (CID) in the capillary skimmer regionby applying the appropriate potentials between the capillary exitelectrode 39 and skimmer 38. In addition, the analytical steps of iontrapping and/or single or multiple step mass to charge selection with orwithout ion CID fragmentation can be conducted in multipole ion guide 8as described in U.S. Pat. No. 5,689,111 and U.S. patent application Ser.No. 08/694,542. Said mass selection and CID fragmentation steps areachieved by applying the appropriate RF, DC and resonant frequencypotentials to rods or poles 7 of multipole ion guide 8. A continuous orgated ion beam of the resulting ion population in multipole ion guide 8can be transmitted into Time-Of-Flight pulsing region 10 from ion guide8 through electrode or lens orifices 43 and 44.

FIG. 2A through 2D illustrates a progression of steps embodied in theinvention wherein ions trapped in ion guide 8 are gated intoTime-Of-Flight pulsing region 10 and collected on collecting surface 12prior to accelerating said ions into Time-Of-Flight tube drift region20. Referring to FIG. 2A, ions 50 are initially trapped in multipole ionguide 8 by setting a retarding or trapping potential on exit lens 41relative to the DC offset potential applied to ion guide rods 7 as isdescribed in U.S. Pat. No. 5,689,111. A substantially neutral or zerofield is set in pulsing region 10. The retarding potential applied tolens 41 is lowered for a set time period, then reapplied, to gate ionpacket 51 from ion guide 8 into pulsing region 10. The translationalenergy of ion packet 51 is determined by the voltage difference betweenthe ion guide offset potential and the substantially equal voltages seton electrodes 11 and 13. During the period when the ions are being gatedout of ion guide 8, voltages are applied to electrodes or lenses 41 and42 to optimize the ion transfer into pulsing region 10. Ideally, ionstraversing pulsing region 10 prior to pulsing into TOF tube drift region20 should have no velocity component in the direction perpendicular tothe surface of lenses 11 and 13. As this condition is difficult toachieve, alternatively, the initial ion trajectory in the pulsing regionshould be directed such that any orthogonal component of velocity shouldbe correlated to the ion spatial location. Such a condition can beapproximated if ions are directed into the pulsing region as a parallelbeam or from a point source as is described in U.S. patent applicationNo. 60/021,184. In practice, ions contained in ion packet 51 that enterTime-Of-Flight pulsing region 10 have the primary direction of theirinitial velocity parallel to the surface of lenses 11 and 13 with asmall component of velocity in the non parallel or orthogonal direction.The lower the axial velocity component of ion packet 51, the moredifficult it is to optimize the ion trajectory into pulsing region 10.In practice, below 10 eV, it becomes difficult to prevent an increase inthe orthogonal velocity and spatial distribution of ion packet 51 as ittraverses pulsing region 10. In the embodiment of the inventiondiagrammed in FIG. 2, ions traversing pulsing region 10 are directedtoward collecting surface 12 of electrode 11 prior to being pulsed intoTime-Of-Flight tube drift region 20. The collection of ions on surface12 prior to extraction, reduces the initial ion packet spatial andenergy spread in pulsing region 10. By compressing ions on or nearsurface 12 prior to pulsing the ion packet into TOF tube drift region20, energy and spatial distributions of the initial ion packet can beimproved, compared to pulsing from a gas phase primary ion beam. Thesurface collection of ions decouples the TOF pulse from the primary ionbeam velocity or spatial distribution. Consequently, Time-Of Flightresolution can be improved over a wide range of primary ion beamconditions with soft-landing or surface induced dissociation of ions oncollecting surface 12 prior to acceleration into Time-Of-Flight tubedrift region 20. Examples of ion collection and extraction sequencesfrom collecting surface 12 will be described with reference to FIGS. 2through 10.

Depending on the initial length of ion packet 51 as determined by thegate ion release time, some Time-Of-Flight mass to charge separation canoccur in the primary ion beam as ion packet 51 traverses pulsing region10. By timing the gate ion release time and the travel time of theresulting ion packet into the pulsing region prior to orthogonalpulsing, a portion of the mass to charge scale can be prevented fromentering Time-Of-Flight tube drift region 20 as described in U.S. Pat.No. 5,689,111. As diagrammed in FIG. 2B, Time-Of-Flight separationoccurrs between ions of different mass to charge in initial ion packet51 as ion packet 51 traverses pulsing region 10 forming separate ionpackets 52 and 53. Lower mass to charge ions comprising ion packet 53have a higher velocity than the higher mass to charge ions comprisingion packet 52 causing mass to charge separation as initial ion packet 51traverses pulsing region 10. FIG. 2B shows the point in time where theneutral field in pulsing region 10 has been switched to a field thatdirects the ions in packets 52 and 53 toward electrode 11 and collectingsurface 12. Ions in packet 53 are beyond the usable pulsing regionvolume and are eliminated from any subsequent extraction intoTime-Of-Flight tube drift region 20. This is desirable in someanalytical applications where lower mass to charge ions that are not ofinterest can deaden detector channels prior to the arrival of highermass to charge ions at the detector surface for a given TOF pulse.Removing lower mass to charge ions in a TOF pulse can increase thesensitivity and reproducibility of higher mass to charge ion detectionfor a given analysis. Ion packet 52 is directed toward collectingsurface with a preset energy to achieve a soft-landing landing of ionsor surface induced dissociation fragmentation of ions in ion packet 52.The energy of impact will be determined by the combination of theparallel and orthogonal kinetic energy components at the point when theion impacts the surface. The ion orthogonal velocity component at impactis determined by, the collecting electric field applied in pulsingregion 10, and the initial ion position in pulsing region 10 when thecollecting electric field is applied. The impact energy of the ion oncollecting surface 12 will also be affected by the degree of spacecharge present on the surface, particularly when collecting surface 12is configured with a dielectric material. It may be desirable for acollecting surface to maintain some degree of space charge to facilitatethe extraction of ions directed toward or collected on collectingsurface 12.

After applying a collecting or reverse electric field in pulsing region10 for a set time period, the electric field is reversed in pulsingregion 10. FIG. 2C shows the initial position of ion packet 55 comprisedof soft-landed ions or SID fragment ions located on or near collectingsurface 12 just as the forward accelerating electric field is applied inpulsing region 10. Referring to FIG. 2D, the applied forward ionaccelerating electric field extracts ion packet 56 from collectingsurface 12 and directs the ions comprising ion packet 56 intoTime-Of-Flight tube drift region 20. The ion trajectory may be alteredby applying a non-zero electric field between steering electrodes 15 and16. In this manner the ions comprising extracted ion packet 56 may bedirected to impact on detector 22 or 23. In one embodiment of theinvention, the timing and application of voltages to electrodes 41, 42,11, 13, 15 and 16 are controlled by the configuration of power supplies,switches and controllers as diagrammed in FIG. 4. FIGS. 5A and 5Bdiagram one embodiment of the invention wherein the collecting surfaceis configured with multiple dielectric and conduct layers. With timingcoordinated with switch controller 62 in FIG. 4, voltages are switchedbetween conductive layers to remove the image charge formed on thereverse side of the dielectric collecting surface layer. Rapid removalof the image charge aids in releasing trapped ions from the collectingsurface during the forward ion accelerating step.

One embodiment of the invention is shown in FIG. 4 where collectingsurface 88 or the conductor backing collecting surface is electricallyisolated from electrode 91 as is diagrammed in FIG. 5A and 5B. Voltagesprovided by power supplies 65, 66 and 67 are selectively applied tocollecting surface 88 or to conductor 271 backing collecting surface 88through switch 61. The outputs of power supplies 65, 66 and 67 areconnected to switch poles 77, 69 and 78 respectively. The voltageapplied to switch output 93 connected to collecting surface 88, iscontrolled by controller 62 through switch control line 75. Voltagesfrom power supplies 66 and 67, connected through lines 71 and 72 topoles 73 and 80 respectively of switch 70 are selectively applied toelectrode 91 through output 98 of switch 70. The voltage applied toelectrode 91 is controlled by switch controller 62 through control line76. Switch 60 applies voltages from power supplies 63 and 64, connectedto poles 68 and 79 respectively, to switch output 92 connected to exitlens 41. Switch controller 62 sets the output of switch 60 throughcontrol line 74 to control the gating or release of trapped ions frommultipole ion guide 8. Voltages from power supplies 81 and 82, connectedto poles 85 and 84 respectively of switch 83 are applied to lens 13through switch 83 output connection 94. The voltage applied to lens 13is controlled by switch controller 62 through control line 86. In theembodiment shown, lens 14 is tied to ground potential and voltage isapplied to lens 42 from power supply 97. Steering lenses 15 and 16 areconnected to power supplies 95 and 96 respectively. In the embodiment ofthe invention diagrammed in FIG. 4, the potentials of lenses 42, 14, 15and 16 remain constant during an ion surface collecting and extractioncycle as diagrammed in FIG. 2.

Switches 60, 61, 70 and 83 are synchronously controlled by switchcontroller and timer 62. The pole positions of switches 60, 61, 70 and83, as diagrammed in FIG. 4 are set to allow the gating or release oftrapped ions from ion guide 8. The voltages set on power supplies 63,97, 66, and 81 connected to electrodes or lenses 41, 42, 88 with 91 and13 respectively, optimize the initial release of ion packet 51 from ionguide 8. After the gate ion release time period is over, controller 62switches output 92 of switch 60 to power supply 64 through pole 79 toend the release of ions from ion guide 8. FIG. 2A illustrates theposition of released ion packet 51 shortly after output 92 of switch 60has been switched from power supply 63 to 64. Variations of trapping andreleasing ions from ion guide 8 are described in U.S. Pat. No. 5,689,111and these alternative means for ion trapping and release can be equallyconfigured in the invention described herein. After an appropriate delayto allow the desired portion of ion packet 52 to move into position overcollection surface 88 or 12 as shown in FIG. 2B, controller 62 switchesoutput 93 from power supply 66 to 65 through switch 61. This switchingof voltages changes the substantially neutral or zero electric field inpulsing region 10 to a reverse electric field that directs ions towardcollecting surface 88. For positive ions, the voltage applied to powersupply 65 will be less or more negative than the voltage applied toelectrodes 91 and 13. The impact energy of ions with collecting surface88 will be a function of the amplitude of the relative voltages appliedto electrodes 13, 91 and 88 and the initial ion energy in the orthogonaldirection prior to impacting on collecting surface 88. Higher impactenergy may be applied to cause surface induced dissociation or a lowerenergy impact may be set to allow soft-landing of ions on collectingsurface 88. As shown in FIG. 5A, collecting surface 88 may be configuredas a subset of the total area of pulsing region electrode assembly 90.

During the reverse field or surface collecting step, the output of powersupply 65 is applied directly to collecting surface 88 if collectingsurface 88 is a conductive or a semiconductor material. If collectingsurface 88 is comprises a dielectric material, voltage is applied to aconductor backing the dielectric surface. FIG. 5B is a side viewdielectric collecting surface 88 backed by conductor 271. As diagrammedin FIG. 5A and 5B, electrode 91 and collecting surface 88 of electrodeassembly 90 are configured as a planar surface. Ion collecting surface88 or conductor 271 backing collecting surface 88 is electricallyisolated from electrode 91. The voltage applied to electrode 91 ofelectrode assembly 90 during the reverse field conditions can be set tobe substantially equal to the voltage applied to lens of electrode 13.Alternatively, a voltage different from that applied to electrode 13 canbe applied to electrode 91 that to optimize the ion collection orfragmentation conditions during the surface collection step. Due theelectric field between collecting surface 88 and lens portion 91, ionsare directed substantially toward collecting surface 88 during reversefield conditions. The size and position of collecting surface 88 isconfigured to maximize the detection efficiency of ions accelerated fromsurface 88 into TOF tube drift region 20. Ions that are initiallyspatially dispersed in Time-OF-Flight pulsing region 10 are spatiallycompressed on the surface area of collecting surface 88 prior toaccelerating the ions into Time-Of-Flight tube drift region 20. Theinitial velocity distribution of the ion beam traversing pulsing regioncan be reduced by collection on or near surface 88 prior to accelerationinto time-of-flight drift region 20. Collecting surface 88 can beconfigured as a conveniently replaceable surface. Different surfaces maybe interchanged to optimize performance for a desired analyticalapplication. Surfaces may be comprised of conductor materials, bulkdielectric materials such as Teflon, Kapton, self assembled monolayerchemistries or piezo electric materials.

Referring to FIG. 4, output 93 is switched to power supply 65 for adesired time period. The collecting time period will vary depending onthe field applied in pulsing region 10, the desired time for ions tospend in contact or in the vicinity of the surface and whether it isdesired to collect all ions initially positioned in pulsing region or aportion of the ions on surface 88 prior to accelerating ions intoTime-Of-Flight tube drift region 20. If collecting surface 88 iscomprised of either a dielectric or a self assembled monolayer (SAM)material, the space charge created by ions initially collected onsurface 88 may prevent additional ions from touching the surfaceunder-soft landing conditions. Miller et. al., Science, Vol. 275, 1447,1997, reported that an ion soft-landed on an F-SAM surface remainsintact without loss of charge for hours when kept under vacuum. Theretention of ion charge on the surface can be desirable in someanalytical applications. The initial space charge created allows ions tobe accelerated toward the collecting surface with compression of theinitial ion packet spatial and velocity distribution while preventingions from touching the surface prior to being accelerated intoTime-Of-Flight tube drift region 20. Some degree of space chargingmaintained on the collecting surface facilitates removal or extractionof ions subsequently accelerated toward the surface because the spacecharge prevents the approaching ions from forming a bond with thesurface. The collecting surface can be initially charged by conductingone or more initial surface collection cycles. Depending on the surfacematerial used and the initial ions soft-landed, such soft-landed ionsmay not release with the reversal of the collecting electric field inpulsing region 10. In this manner an effective surface space chargesteady state can be reached which enables very high ion yield from eachsubsequent soft landed surface collection cycle. Any small non-uniformfield created by the space charge which would effect trajectories ofions traversing pulsing region 10 can be counteracted by applying theappropriate bias voltage to electrode 13 from power supply 81.Collecting and releasing ions from a dieletric surface with minimalspace charge buildup can be achieved by controlling the complimentaryimage charge that plays a role in holding ions at a dielectric surface.

FIG. 5B is a diagram of one embodiment of the invention where electrodeassembly 90 comprises a multiple layer collecting surface assembly.Dielectric collecting surface 88 is backed by conductive layer 271,dielectric layer 272 and conductive layer 273. Soft-landed or SIDfragment ions that remain in contact with pulsing region side 277 ofcollecting surface 88 form an image charge on the reverse side ofdielectric collecting surface 88. The image charge is delivered throughconductive layer 271. Take the case of positive ion operating mode wherethe potential applied to electrode 13 is more positive than thepotential applied to electrode 271 so that positive ions are directedtoward collecting surface 88 during the ion surface collecting step. Forsoft-landing conditions consider the voltages applied to electrodes 13,19 and 271 to be +8, +2 and 0 V respectively. During the ion collectionstep, the voltage applied to conductive layer 273 from power supply 67is +450 V. With +450 V applied to one side of dielectric layer 272, anegative image charge is retained along conductive surface layer 271.Dielectric and conductive layers 88, 271, 272 and 273 form a two layercapacitor assembly. Just as a forward accelerating voltage is applied inpulsing region 10, switch 275 applies voltage (0 V) from power supply 65to conductive layer 273 through connection 276. The +450 voltage frompower supply 67 is applied to conductive layer 271 through switch 61 andto electrode 90 to accelerate the ions collected on or near collectingsurface 88 through the grid of electrode 13. The timing of the voltageswitching is controlled by controller 62. The rapid release of chargethrough conductive layer 271 is aided by the rapid charge shift in thecapacitor formed by layers 271, 272 and 273. The rapid potential changeof conductive layer 271 reduces the image charge helping to hold thepositive ions on collecting surface 88. The rapid reduction of imagecharge coupled with a forward biased accelerating field aids inovercoming the attractive forces holding the ions to the collectingsurface and moving the ions into pulsing region 10 in the gas phase.Voltage polarities given for the positive ion example would be reversedfor negative ion operation.

Alternatively, if collecting surface 88 was comprised of a singledielectric layer the image charge for positive ion collection could bedelivered to the reverse side of collecting surface 88 by exposure to anelectron beam during the ion collection step. Rapid removal of anegative image charge can be achieved by impinging the back side ofcollecting surface 88 with positive ion beam such as Xe+ ions at theonset of the forward accelerating field in pulsing region 10. Fornegative ion collection the positive ion beam can supply the imagecharge and the electron beam can be used to rapidly neutralize the imagecharge on the back side of collecting surface 88 when the forwardaccelerating field is applied in pulsing region 88. Depending on theamount of charge collected on collecting surface 88, it may be desirableto neutralize the image charge with a small delay before applying theforward accelerating field. This timing delay helps to decouple the ionextraction from the forward ion accelerating step minimizing the effectsof space charge on the ion TOF flight time. The sequence of ion surfacecollection, rapid image charge reduction and acceleration of ions intoTOF tube drift region 20 can occur at a rate of over 20,000 times persecond limited by the heaviest ion mass to charge flight time. Usinghigher TOF pulse rates, the space charge buildup on collecting surface88 per pulse is minimized for typical ion beam flux densities deliveredfrom API sources. Consequently, the affects of collecting surface spacecharge on TOF ion flight time can be reduced or effectively eliminatedby maintaining sufficiently high TOF pulse rates.

In another embodiment of the invention as diagrammed in FIG. 6,electrode assembly 102 comprises electrode 101 and collecting surface100. Electrode surface 100 is configured with piezo material. Byapplication of an electric field across the piezo material ormechanically stressing the piezo material in the proper direction, theamount of charge maintained on collecting surface 100 can be controlledto prevent ions of like charge from touching collecting surface 100during soft-landing operation. Any voltage applied across the piezomaterial of collecting surface 100 can be electrically referenced orfloated on the output of switch 61. Voltage is applied to collectingsurface 100 relative to the voltage applied to electrodes 101 and 13 todirects ions located in pulsing region 10 towards surface 100. The localcharge present on surface 100 due to a stressed piezo ceramic state canprevent ions from touching the surface. Ions accelerated toward thecharged collecting surface with sufficient velocity to overcome thelocal surface charge repulsion can impact the surface resulting insurface induced dissociation fragmentation. Local surface charge of thesame polarity as approaching ions can result in reduced ion to surfacecharge exchange yielding a higher percentage of fragment ions. Piezosurface 100 may be configured from a number of materials and shapesincluding but not limited to a single material such a quartz orassemblies of materials such as PZT ceramic with layered conductors. Forexample, collecting surface 100 can be configured as a portion of onesurface of a planar PZT bimorph where a conductive layer covers thebimorph surface accept for the area defined by collecting surface 100.In this manner a voltage can be applied across the bimorph assemblymechanically stress the crystal, resulting a surface charge on ceramiccollecting surface 100. The surface polarity can be reversed bystressing the PZT bimorph in the opposite direction. Time-of-flight masscalibration can be performed after stressing the piezo material toaccount for any movement of collecting surface 100. Electrode 101 iselectrically isolated from the piezo material to allowing theapplication of different voltages between collecting surface 100 andelectrode 91. Relative voltages can be set between electrode 91 andcollecting surface 100 to create a potential well that prevents surfacecollected ions from drifting or skating off the edges of collectingsurface 100 prior to accelerating said ions into TOF tube drift region20.

Space charge a the collecting surface can facilitate the release of SIDfragment ions from the surface the electric field in the pulsing regionis reversed. Depending on the SID ion fragmentation application, it maybe desirable hold the reverse electric field for a given delay after allions have initially impacted the collecting surface. This reverse fieldtime delay after ion impact would stop or reverse the velocity of anyparent or fragment ions reflected or scattered from the surface afterSID. Winger et. al. reported that the average kinetic energydistributions of the product ions scattered from aklyl-monolayersurfaces after a 25 eV impact of the parent ions, ranged from 6 to 8 eVdepending on the ion species and impact conditions. Delaying theapplication of the extraction or forward accelerating field would reducethe initial scattered product ion energy spread, improvingtime-of-flight resolution. The addition of a laser pulse directed ontocollecting surface 88 after the reverse field is removed and theaccelerating field is applied can also be used to promote ion releasefrom collecting surface 88. The timing of the laser pulse and theapplication of the accelerating electric field reversal can becontrolled to minimize the released ion spatial and energy spreadresulting in higher time-of-flight resolution. The energy spread of ionsreleased from the collecting surface with a laser pulse can be reducedby maintaining the reverse or surface collecting field for a shortperiod of time prior to the application of the ion accelerating field inpulsing region 10.

A forward accelerating field is applied in pulsing region 10 after thereverse or collecting field has been held for a period of time. Theaccelerating field accelerates ions on or near collecting surface 88into Time-Of-Flight tube drift region 20. As described above, theaccelerating field may applied in conjunction with or after a laserpulse is directed onto collecting surface 88 to aid in the aid in therelease of ions from collecting surface 88. Referring to FIG. 4, therapid application of a forward accelerating field is achieved bysimultaneously switching the output of power supply 67 to collectingsurface 88 and electrode 91 through switches 61 and 70 respectively andthe output of power supply 82 to electrode 13 through switch 83. Theaccelerating field accelerates ions on or near collecting surface 88into Time-Of-Flight tube drift region 20. Switch 60 retains its stateand the outputs of power supplies 97, 95 and 96 remain unchanged. Theforward accelerating field applied in pulsing region 10, is maintainedfor a time period sufficient to allow the highest mass to charge ofinterest, to pass through the grid of ion lens 14 and intoTime-Of-Flight tube drift region 20. After the applied forwardacceleration field time period is complete, the controllersimultaneously switches switch 83 from pole 84 to 83, switch 70 frompole 80 to 73, switch 61 from pole 78 to 69 and switch 60 from pole 79to 68. This forms a substantially neutral field in pulsing region 10 andopens the gate to release ions from ion guide 8. This switch eventbegins a new ion gating, surface collection and TOF forward accelerationcycle. Controller 62, the power supplies and switches are configured toallow rapid rise time of the voltages applied to electrodes or lenses41, 88, 91 and 13. The voltage rise time applied to electrodes 41, 88,91 and 13 is generally less than 50 nanoseconds to achieve optimalTime-Of-Flight performance.

Variations to the ion surface collection and TOF pulsing cycle describedcan be configured by modifying the switching sequence and time delays ascontrolled by controller 62 to optimize performance for a givenanalytical application. For example, it may be desirable to configuremore than one ion gating and surface collection cycle prior toaccelerating ions into the time-of-flight drift region. Multiple gatingand surface collection cycles may serve to accumulate ions on collectingsurface 88 prior to extraction. Soft-landing surface collection cyclescan be mixed with SID steps prior to ion extraction. The build up ofsurface space charge can be controlled in this manner or ion-surfacereactions can be studied where the first packet of gated ions isaccelerated to the collecting surface having a different compositionthan the ion packets that are surface collected from subsequent gatedion release cycles. Surface collected ions can retain their charge for aperiod of time when soft-landed on F-SAM or other dielectric surfacesallowing different ion populations supplied from pre-gated mass tocharge selection or fragmentation steps to be sequentially collected orreacted on the collecting surface prior to extraction and accelerationinto Time-Of-Flight tube drift region 20. In all configurations of theinvention, ions with either positive or negative polarities can bedirected toward collecting surface 88 or 100 with the appropriatepolarity electric field applied in pulsing region 10. Similarly, theappropriate polarity electric field can be applied to extract positiveor negative ions collected on or near collecting surface 88 or 100 andaccelerate said ions into Time-Of-Flight tube drift region 20.Collecting surfaces 88 and 100 can be configured to be automaticallyreplaced without breaking vacuum. With automated exchange from a set ofcollecting surfaces, a given collecting surface material can be rapidlyconfigured to optimize performance for a given application. When thevacuum is vented, a single or a set of collecting surfaces can beremoved and reinstalled manually by removal and reinstallation of vacuumflange assembly 49. Alternatively, collecting surface 88 can beconfigured as part of a continuous ribbon or belt. Collecting surface 88can be refreshed by moving a portion of the belt through the collectingsurface area. The belt can be moved periodically or continously topresent a fresh surface at the location of collecting surface 88 duringTime-Of-Flight operation. The belt can be configured with dielectric,conductive or semiconductive materials with or without SAM surfacecoatings.

Another embodiment of the invention is diagrammed in FIG. 3. Ions from acontinuous beam enter pulsing region 110 from a substantially orthogonaldirection while a reverse electric field is applied between electrode orlens 113 and electrode 111 and collecting surface 112. As shown in FIG.3A, ions comprising continuous primary ion beam 150 enter pulsing region110 from multipole ion guide 108 and are directed to collecting surface112 in the presence of this reverse electric field. Ions are accumulatedon or near collecting surface 112 for a period of time after whichadditional ions are prevented from entering pulsing region 110 asdiagrammed in FIG. 3B. Continuous beam 150 can be stopped by applying aretarding or trapping potential to exit lens 141 which prevents ionstraversing multipole ion guide 108 from exiting through exit lens 141.FIG. 3B illustrates the breaking of continuous beam 150 by applying atrapping potential to exit lens 141 and/or a combination of lens 141 and142. The ions in truncated primary ion beam 152 continue into pulsingregion 110 and are directed toward collecting surface 112. When the ionsin pulsing region 110 have been collected on or near collecting surface112, as represented by ion packet 153 in FIG. 3C, a forward acceleratingelectric field is applied between collecting surface 112 with electrode111 and electrode 113. The forward accelerating electric field extractsions in ion packet 153 from collecting surface 112 and released ionpacket 154 is accelerated through the grids of electrodes of lenses 113and 114 into Time-Of-Flight tube drift region 120 as diagrammed in FIG.3D. Voltages can be applied to steering lenses 115 and 116 to steer thedirection of the ions as ion packet 154 moves into Time-Of-Flight driftregion 120. In the continuous beam embodiment of the invention asdiagrammed in FIG. 3, ions are trapped or accumulated on collectingsurface 112 with less time spent per cycle trapping ions in ion guide108. High duty cycle can be achieved with this continuous beamembodiment of the invention because few ions are lost throughout the ionsurface collection and extraction cycle. This is an alternative to theembodiment of the invention as diagrammed in FIG. 2, wherein more timeis spent accumulating or trapping ions in ion guide 8 prior tocollection on collecting surface 12. One embodiment or the other mayyield optimal performance depending on the analytical application.

Electrode 145 may be added to pulsing region 110 as shown in FIG. 3 toprovide a retarding potential to the primary ion beam. The kineticenergy, primarily in the axial direction, of ions in primary beam 150 asthey enter pulsing region 110 is set by the voltage difference betweenthe ion guide offset potential and the average field applied toelectrodes 111 and 113 traversed by the primary ion beam. A voltage maybe applied to electrode 145 to reduce the primary ion beam axialvelocity as the ions traverse pulsing region 110. In soft landingsurface collection operation it may be desirable to reduce the ionimpact energy on the surface. The ion impact energy on the collectingsurface is a function of the primary beam axial velocity component andthe orthogonal component due the reverse collecting field applied inpulsing region 110. Configuring electrode 145 to retard the primary ionbeam axial velocity component allows more precise control of the ionimpact energy with collecting surface 112. Reducing the primary ion beamenergy by lowering the potential of the ion guide offset relative tothat of electrodes 111 and 113 reduces the ability to shape and directthe primary ion beam it enters pulsing region 110. Local fringing fieldspresent in the path of the primary ion beam path prior to enteringpulsing region 110 have a more pronounced and detrimental effect onfocusing of the primary ion beam when the ion kinetic energy is reduced.Applying a retarding potential to electrode 145 during collection ofions on surface 112 allows the setting of the initial primary beamkinetic sufficiently high to achieve efficient transport from ion guide108 into pulsing region 110. The potential applied to Electrode 145provides an additional degree of control of the ion impact energy onsurface 112 independent of the primary ion beam energy. When a forwardaccelerating potential is applied in pulsing region 110, the appropriatevoltage is applied to electrode 145 to match the field that would appearat its position were it not present. With such a potential appliedduring ion acceleration into TOF tube drift region lens 145 does distortthe optimal accelerating field established by potentials applied toelectrode 111, surface 112 and electrode 113.

The power supply and voltage switching embodiment shown in FIG. 4 can beconfigured to control the continuous ion surface collection andextraction sequence diagrammed in FIG. 3. Replaceable collecting surface112 and electrode 111 can be configured as diagrammed in FIGS. 5 or 6 asdescribed for the embodiment of the invention diagrammed in FIG. 2. Inparticular, surface space charge formed from ion accumulation on adielectric or a Self Assembled Monolayer surface can be used to aid inion extraction from the surface or to prevent soft landed ions fromcontacting the surface prior to acceleration into Time-Of-Flight tube120. It is preferable to maintain the magnitude to the surface spacecharge at a reproducibly low level to minimize the effect of the spacecharge repelling force on an accelerated ion flight time. As wasdescribed for the embodiment diagrammed in FIG. 2, a laser pulseimpinging on collecting surface 112 may also be used to aid in therelease of ions collected on collecting surface 112. The timing of thelaser pulse and the application of the forward ion accelerating fieldcan be configured to provide optimal Time-Of-Flight mass analyzerperformance.

An alternative embodiment of the invention is the configuration ofcollecting surface 88 in FIG. 5A coated with an appropriate matrixmaterial, as is known in the art, to enable Matrix Assisted LaserDesorption Ionization (MALDI) of ions collected on collecting surface88. Ions produced from an external ion source are collected on surface88 as described above. A laser pulse with the optimal wavelength, powerand duration is directed to impinge on collecting surface 88 to produceMALDI generated ions. The MALDI produced ions are then accelerated intothe Time-Of-Flight tube with or without delayed extraction. If theexternal source is an Electrospray ionization source interfaced on-lineto a liquid chromatography system, ions generated from the ES source aredelivered to the collecting surface in the Time-Of-Flight pulsingregion. The ions may be soft-landed or accelerated to the collectingsurface with sufficient energy to cause surface induced dissociationfragmentation. The surface collected ion population may or may not beneutralized depending on the MALDI matrix material used. A laser pulseimpinging on the collection surface releases ions and/or re-ionizessurface neutralized ions prior to acceleration of the product ions intothe Time-Of-Flight tube drift region. Combining surface collection ofAPI source generated ions with subsequent MALDI of said surfacecollected ions and surfaced neutralized molecules, allows MALDI massspectra to be generated on line from LC or CE separations. ATime-Of-Flight mass analyzer can be configured according to theinvention whereby ES and MALDI mass spectra can be alternativelygenerated on-line during an LC-MS or a CE-MS run. MALDI generated ionsof higher molecular weight generally have fewer charges than ESgenerated ions from the same compounds. Depending on the configurationof the collection surface material multiply charged ions produced by ESionization may have a reduction in the number of charges per ion onimpact with the collecting surface. Charge reduction may be desirable insome applications as it spreads ion peaks out along the mass to chargescale, reducing peak complexity.

One aspect of the invention is configuration of heating or cooling ofcollecting surface 88 as diagrammed in FIG. 5A. Cooling of collectingsurface 88 can aid in the condensing of more volatile ions on thesurface prior to pulsing into the Time-Of-Flight tube drift region. Areduced surface temperature may also aid in slowing down chemicalreactions at the surface or decrease the rate of ion charge exchangewith the surface. Heating collecting surface 88 can aid in the releaseof ions from the collecting surface when a forward accelerating field isapplied. Surface to ion reaction rates may be enhanced by heating thecollecting surface in selected applications. Thermal fragmentation ofions can occur when ions land on a heated surface. Temperature cyclingof the collecting surface during sample introduction to an API sourcecan add a useful variable to surface reaction studies with subsequentTime-OF-Flight mass to charge analysis.

An alternative embodiment of the invention is diagrammed in FIGS. 7Athrough 7D. Referring to FIGS. 7A and 7B, ions produced in vacuum froman ion source located outside Time-Of-Flight pulsing region 160 aredirected into pulsing region 160 and collected on collecting surface161. As an example of an ion source which produces ions in vacuum, FIG.7 diagrams a Laser Desorption (LD) or Matrix Assisted Laser DesorptionIonization source mounted in the Time-Of-Flight vacuum region such thations produced from a laser pulse are directed into Time-Of-Flightpulsing region 160. Removable multiple sample stage 163 positions sample164 in line with laser pulse 167 generated from laser 166. In theembodiment shown, sample stage assembly 163 is configured whereby theposition of sample 164 relative to laser pulse 167 can be adjusted toachieve maximum sample ion yield per laser pulse. Ions released fromsample 164 due to an impinging laser pulse, are extracted with anextraction or accelerating potential applied between sample stage 163and electrode or lens 165. Alternatively, delayed ion extraction fromregion 168, between electrode 165 and sample surface 164, can beachieved when a neutral field or a weak retarding field is applied for aperiod of time during and subsequent to the laser pulse hitting samplesurface 164. After the delayed extraction time period, the ionextracting electric field is applied to region 168 between electrode 165and sample stage 163 to accelerate ions from region 168 into pulsingregion 160. Whether the ions are extracted from region 164 with aconstant accelerating field or subsequent to a delayed extraction timeperiod, the ions are accelerated into Time-Of-Flight pulsing region 160with the ion packet primary velocity component oriented in a directionsubstantially parallel to the surface of lens or electrode 169. In theembodiment diagrammed in FIG. 7B, MALDI generated ions from sample 164enter pulsing region 160 with trajectories generally orthogonal to theaxis of Time-Of-Flight drift region 171.

A substantially neutral electric field is maintained in pulsing region160 as the ions produced from laser pulse 167 traverse the pulsingregion. The ions produced from laser pulse 167 and accelerated intopulsing region 160 are diagrammed as ion packets 172 and 173 in FIG. 7B.Ion packet 173 is comprised of the lower mass to charge ions, such asmatrix related ions, created by laser pulse 167 impinging on sample 164.The lower mass to charge ions in ion packet 173 have a higher velocitycomponent than the higher mass to charge ions comprising ion packet 172.Ions of different mass to charge experience some degree ofTime-Of-Flight separation as they traverse pulsing region 160. After aselected time period subsequent to laser pulse 167, a reverse electricfield is applied in Time-Of-Flight pulsing region 160 to direct theMALDI generated ions comprising ion packets 172 and 173 to move towardscollecting surface 161 and electrode 162. The time delay prior toinitiating surface collection can be chosen such that undesired lowermass to charge ions have time to move beyond pulsing region 160 when thereverse electric field is applied. As diagrammed in FIG. 7C, higher massto charge ions from ion packet 172 are collected on collecting surface161 while the lower mass to charge ions form ion packet 173 impact onelectrode 162 and are not collected on collecting surface 161. When thereverse field has been applied for a time period sufficient to collections on or near collecting surface 161, a forward accelerating electricfield is applied in pulsing region 160 between electrode 169 andcollecting surface 161 and electrode 162. As shown in diagrammed in FIG.7D, the forward ion accelerating field accelerates ions collected on ornear collecting surface 161 into Time-Of-Flight drift tube region 171. Alaser pulse can be applied to collecting surface 161 to aid in therelease of ions from collecting surface 161.

The voltage switching sequence described for the MALDI ionization step,ion acceleration into pulsing region 160, surface collection of ions andsubsequent acceleration of surface collected ions into Time-Of-Flighttube drift region 171, is similar to that described for the embodimentof the invention described in FIGS. 2 and 4. Individual power supplyoutputs can be applied to electrodes or lenses 163, 165, 162, collectingsurface 161, and 169 through switches synchronized with a switchcontroller with timer. The assembly comprising collecting surface 161and electrode 162 can be configured as diagrammed in FIGS. 5 or 6depending on the analytical application requirements. Ions can beaccumulated on collecting surface 161 from one or more MALDI pulsesprior to accelerating the surface collected ions into Time-Of-Flightdrift region 171. Depending on the collecting surface material selected,surface space charge can be used to prevent incoming ions from touchingthe surface during soft landing surface collection, facilitating thesubsequent ion extraction and acceleration into Time-Of-Flight tubedrift region 171. Removable collecting surface 171 can be comprised ofbut not limited to conductive, insulating, Self Assembled Monolayer,semiconductor or piezo materials. Collecting surface holder assembly 178can be configured to allow automatic changing of collecting surface 161without breaking vacuum. Collecting surface materials can be switched topresent the optimal collecting or fragmentation surface for a givenapplication.

By adjusting the reverse electric field strength in pulsing region 160,MALDI produced ions can be directed to collecting surface 161 withenergy sufficient to cause surface induced dissociation or soft landedwith minimal fragmentation. Controlled SID ion fragmentation can beachieved for MALDI generated ions by selection of the relative voltageapplied between electrode 169 and electrode 162 and collecting surface161. MALDI generated ions moving from region 168 to surface 161 willspend sufficient time traversing pulsing region 160 to exhaust fast ionfragmentation processes that occur in MALDI ionization. Surfacecollection of MALDI generated ions reduces the chemical noise appearingin MALDI TOF mass spectra due to fast ion fragmentation processes thatoccur in MALDI ionization. With surface collection of MALDI generatedions, ion fragmentation processes are be completed prior acceleratingthe surface collected ions into Time-Of-Flight tube drift region 171.This results in higher resolution over a wider mass to charge range andeasier to interpret mass spectra. All MALDI produced ions can be surfacecollected, if it is not desirable to eliminate ions in portions of themass to charge scale. Lower mass to charge ions generated from the MALDImatrix may be eliminated using reverse field delayed extractiontechniques in region 168 or with Time-Of-Flight separation in pulsingregion 160 prior to surface collection as was described above. Analogousto the embodiment diagrammed in FIG. 3, MALDI produced ions can becontinuously collected by the continuous application of a reverse and aretarding electric field in pulsing region 160 during the time periodwhen MALDI produced ions are accelerated from region 168 into pulsingregion 160. In this manner, all MALDI produced ions are collected on ornear collecting surface 161 prior to being accelerated intoTime-Of-Fight tube drift region 171.

Any vacuum ion source can be substituted for the Laser Desorption orMALDI ion source diagrammed in FIG. 7 where ions enter pulsing region160 with a trajectory substantially orthogonal to the Time-Of-Flighttube axis. Alternatively, ions produced from atmospheric pressure ionsources or vacuum ion sources can be configured such that the ionsproduced, need not be directed into time-of-flight pulsing region 10,110 or 160 with a trajectory that is substantially orthogonal to theTime-Of-Flight tube axis. Alternative embodiments of the invention arediagrammed in FIGS. 8 and 9 wherein a MALDI ion source is configuredsuch that the sample surface is positioned in front and behindcollecting surfaces 180 and 212 respectively. Referring to FIG. 8, laserpulse 183 from laser 182 is directed onto sample 181 mounted onremovable sample holder 184. Ions produced from laser pulse 182 areaccelerated from region 186 into pulsing region 188 by applying theappropriate voltage, with or without delay extraction, to electrode 185.The MALDI generated ions pass through pulsing region 188 and arecollected on replaceable collecting surface 180. Ions collected on ornear collecting surface 180 are subsequently extracted from collectingsurface 180 and accelerated into Time-Of-Flight tube drift region 191.Analogous to the continuous ion beam surface collection sequencediagrammed in FIG. 3, a reverse electric field is maintained betweenelectrode 189 and collecting surface 180 and electrode 192 to directions accelerated from region 186 toward collecting surface 180. Ionsproduced from laser pulse 183 can be immediately accelerated intopulsing region 188 or the ions produced can be accelerated into pulsingregion 188 after a delayed extraction period. Direct acceleration ordelayed extraction from region 186 is controlled by the voltage appliedto lens 185 relative to the voltage applied to electrically isolatedsample holder 184 during and subsequent to the impinging of laser pulse183 on sample 181. Ions collected on collecting surface 180 areextracted from collecting surface 180 and accelerated through lenses 189and 190 into Time-Of-Flight tube drift region 191 by applying a forwardaccelerating field between electrodes 189 and collecting surface 180 andelectrode 192 in Time-Of-Flight pulsing region 188. Multiple laser pulseand collecting steps may precede an ion accelerating pulsing intoTime-Of-Flight tube drift region 191.

An alternative ion source mounting configuration is diagrammed in FIG. 9wherein a MALDI ion source is positioned behind collecting surface 212.Laser pulse 203 produced from laser 202 impinges on sample 200 mountedon removable sample holder 210 releasing ions into region 205 above thesample surface. Ions located in region 205 are accelerated, with orwithout delayed extraction, into Time-Of-Flight pulsing region 211 byapplying the appropriate voltages electrode 201 and sample holder 210. Areverse electric field is applied between electrode 207 and collectingsurface 212 and electrode 206 in pulsing region 211 to direct iontrajectories toward collecting surface 212. Ions directed towardcollecting surface 212 will form reversing curved trajectories 204 priorto approaching or impacting on collecting surface 212. In thisembodiment of the invention, the relative positions and geometries ofion source 213 and Time-Of-Flight pulsing region 211 with collectingsurface 212 can be configured in a manner that a spatial dispersion ofions can occur on collecting surface 212 based on the initial ion energyand trajectory. This ion surface position dispersion can be used toselectively eliminate a portion or portions of the initially producedion population from being subsequently accelerated into Time-Of-Flighttube drift region 208. Depending on the size of collecting surface 212,ions of only a selected initial ion energy and trajectory will becollected prior to acceleration into Time-Of-Flight tube drift region208. Initial ion energy can be selected by setting the appropriateelectric fields in regions 205 and 211 during the surface collectionperiod.

As diagrammed in FIG. 10, sample surface 216 can alternatively bepositioned behind but parallel with collecting surface 215. Collectingsurface 215 configured with an orifice positioned over sample 216 servesas the ion extracting electrode replacing electrode 201 in FIG. 9. Inthe embodiment diagrammed in FIG. 10 the laser is configured to directlaser pulse 217 up the TOF tube to impinge sample 216, producing MALDIgenerated ions. MALDI generated ions entering pulsing region 219 throughorifice 214 in collecting surface 215 are reflected back to collectingsurface 215 by applying a reverse electric field in pulsing region 219.Surface collected ions are subsequently accelerated into theTime-Of-Flight tube drift region by applying an accelerating field inpulsing region 219. In addition, a laser pulse can be applied tocollecting surfaces 180, 212 or 215 to facilitate the release of ionsfrom the collecting surfaces during the ion acceleration step.

Another embodiment of the invention, as diagrammed in Figures 11Athrough 11D, is the configuration of a vacuum ion source that generatesions by Electron Ionization (EI) in Time-Of-Flight pulsing region 231with subsequent surface collection of the ions produced. Ions collectedon or near collection surface 220 are then pulsed into Time-Of-Flighttube drift region 230 where they are mass to charge analyzed. Referringto FIG. 11A, sample bearing gas 229 is introduced into Time-Of-Flightpulsing region 231 through gas inlet tube 223. The neutral gas may bethe output of a gas chromatography column that is introduced into thevacuum maintained in pulsing region 231. Pulsing region 231 andTime-Of-Flight tube drift region may be configured in different vacuumpumping stages in this embodiment of the invention to maintain therequired vacuum pressures in Time-Of-Flight tube drift region 230 whileallowing gas pressures greater than 10⁻⁵ torr in pulsing region 231. Thepressure in pulsing region 231 can be decreased by configuring a pulsedgas inlet valve with gas pulsing synchronized with electron bombardmentionization, surface collection and Time-Of-Flight pulsing cycles. Acontinuous neutral gas source can be used if the pressure in pulsingregion 231 is maintained sufficiently low to avoid ion to neutralcollisions during ion acceleration from collecting surface 220 intoTime-Of-Flight tube drift region 230.

Sample bearing neutral gas from a continuous or pulsed gas sourceintroduced into pulsing region 231 is ionized by electron beam 225,generated from filament and repeller assembly 224. Electron beam 225 isaccelerated into pulsing region 231 when the electric field betweenelectrode 227 and collecting surface 220 and electrode 221 is maintainedsubstantially neutral. After a selected ionization time period, electronbeam 225 is turned off and ions 226 formed in pulsing region 231 aredirected toward collecting surface 220 by applying a reverse electricfield between electrode 227 and collecting surface 220 and electrode221. A pulsed gas source may be closed during the ion surface collectionperiod. FIG. 11B, diagrams the acceleration of ions 226 towardscollection surface 220 when a reverse electric field is applied inpulsing region 231. Ions can be accelerated toward collecting surface220 with energy sufficient to cause surface induced dissociation byapplying the appropriate reverse electric field in pulsing region 231.Alternatively, ions can be soft landed with lower reverse fieldsapplied. Analogous to the apparatus and ion surface collecting methodsdescribed for FIGS. 2, 3, 4, 5 and 6, collecting surfaces may becomprised of but not limited to conductive, dielectric, semiconductor,multilayer, Self Assembled Monolayer or piezo electric materials. Thecollecting surface mounted to vacuum flange 233 is removable and can beconfigured as part of assemblies 90 and 102 as diagrammed in FIGS. 5 and6 respectively. The voltages applied to electrodes 221, 227 and 228 andcollecting surface 220 can be controlled by a power supply and switchconfiguration similar to that diagrammed in FIG. 4. The controller andtimer may also be configured to switch the gas inlet pulsing valve thatcontrols the flow of gas through gas inlet 223. When the EI sourceconfigured in FIG. 11 is operated such that a space charge occurs oncollecting surface 220, soft landed ions can be moved close tocollecting surface 220 without impacting. This method of operationfacilitates the release of ions from collecting surface 220 when forwardion accelerating field is applied in pulsing region 231.

When operating with a gas pulsing valve, ions 232 can be held on or nearthe collecting surface for a period of time to allow a portion of theresidual neutral gas in pulsing region 231 to pump away after the ionsurface collection step. This increases the mean free path and minimizesion to neutral collisions when the ions are accelerated from collectingsurface 220 into the Time-Of-Flight tube drift region for mass to chargeanalysis. FIG. 4C diagrams the point in time just prior to applying theforward accelerating field in pulsing region 231. Neutral gas pressure229 has been reduced during the surface collection time period. Asdiagrammed in FIG. 4D, a forward electric field is applied in pulsingregion 231 accelerating ions from collecting surface 220 through thegrids of electrodes 227 and 228 into Time-Of-Flight drift region 230.Subsequently, a neutral field is reapplied in pulsing region 231 andsample bearing gas is reintroduced into pulsing region 231 and ionizedby Electron Ionization. Multiple EI ionization and surface collectionsteps can precede a forward ion acceleration step. Variations in theionization, surface collection and acceleration sequence can beconfigured with the embodiment of the invention diagrammed in FIG. 11.For example, a laser pulse can be applied to collecting surface 220 tofacilitate the release of ions 232 prior to or during the application ofthe forward accelerating field. If a space charge builds up oncollecting surface 220 for positive ions, the electron beam can bebriefly directed to impinge on collecting surface 220 during each cycleto neutralize desorbed ions. Conversely, for negative ions, electronscan be supplied to collecting surface to create space charge during eachcycle. If reagent gas is introduced into pulsing region 231, sample gascan be ionized with chemical ionization in pulsing region 231. Photon ormultiphoton ionization may also be used to produce ions in pulsingregion 231. The embodiment of the invention as diagrammed in FIG. 11,improves Time-Of-Flight mass analysis resolution and mass accuracy whenoperating with an EI source. Ions created with a large spatial andenergy spread in pulsing region 231, are collected on or near collectingsurface 220, reducing the initial spatial and energy spread prior to ionacceleration into Time-Of-Flight tube drift region 230.

A wide range of ion sources can be configured with the inventionsdescribed herein. Multiple ion source can be configured in a TOF orhybrid TOF mass analyzer. For example, an EI source orthogonal pulsingAPI source and a MALDI source can be configured simultaneously in oneTOF mass analyzer according to the invention. EI or Chemical ionizationsources can be configured external the TOF pulsing region. Theinventions can also be configured with a range of time-of-flightanalyzer configurations that include ion reflectors, steering lenses andmultiple detectors. A variety of vacuum system arrangements can beconfigured with the inventions as well. It is clear to one skilled inthe art that variations in time-of-flight mass analyzers, controlsystems, collecting surface materials, pulsing region geometries, ionsources and hybrid mass analyzers can be configured that fall within thescope of the invention. The invention can also be configured with othermass analyzer types such as Fourier Transform mass spectrometer (FTMS)and three dimensional quadrupole ion trap mass spectrometers. Theinvention can be configured to reduce the ion energy spread of an ionpacket or to cause SID fragmentation of ions prior to transferring theions into the FTMS cell or an ion trap. Higher ion trapping efficiencycan be achieved in FTMS and ion trap mass analyzers when the energy andspatial spread of the primary ion beam is reduced by surface collectionof ions. SID fragmentation allows a higher fragmentation energy than canbe achieved by in the gas phase by CID in either the FTMS cell or iontrap mass analyzer. Combining a SID with FTMS and ion trap massanalyzers extends their range analytical capability. More energeticmeans can also be configured to release ion collected on the collectionsurface such as sputtering with accelerated neutral or ion speciesdirecting a higher energy laser pulse onto the surface while a forwardaccelerating field is applied. These higher energy ion extraction meansmay cause ion fragmentation, damage the surface material or aid chemicalreactions between the ion population and the surface material. In somecases inducing ion to surface compound reactions may be desirable. Inhybrid mass analyzer configurations single or multiple steps of ion massto charge selection, ion fragmentation or ion mobility separation can beconducted prior to directing the resulting ion population to thecollecting surface in the pulsing region of a mass analyzer.

References

The following references are referred to in the present application, thedisclosures of which are hereby incorporated herein by reference:

1. McCormack et. al., Anal. Chem. 1993, 65, 2859-2872.

2. Miller et. al., Science, Vol. 275, 1447, 1997.

3. The Bendix Corporation Research Laboratories Division, TechnicalDocumentary Report No. ASD-TDR-62-644, Part 1, April 1964

4. Wiley et. al., The Review of Scientific Instruments 26(12):1150-1157(1955).

5. Winger et. al. Rev. Sci. Instrum., Vol 63, No. 12, 1992.

6. Wysocki et. al. J. Am. Soc. for Mass Spectrom, 1992, 3, 27-32.

7. Vestal et. al. in U.S. Pat. No. 5, 625,184.

8. Dresch et. al. in U.S. Pat. No. 5,689,111.

9. Dresch in U.S. patent application Ser. No. 60021,184.

Having described this invention with regard to specific embodiments, itis to be understood that the description is not meant as a limitationsince further modifications and variations may be apparent or maysuggest themselves. It is intended that the present application coverall such modifications and variations, including those as fall withinthe scope of the appended claims.

We claim:
 1. An apparatus for analyzing chemical species comprising: aTime-Of-Flight mass analyzer comprising a pulsing region and a detector,said Time-Of-Flight mass analyzer further comprising a collectingsurface within said pulsing region for collection of ions on saidcollecting surface; an ion source that generates ions from a samplesubstance away from said collecting surface; means for directing saidions toward said collecting surface; and means for accelerating saidions into said TOF mass analyzer wherein said surface provides means forcollecting ions on or near said collecting surface.
 2. An apparatusaccording to claim 1 wherein said means for directing said ions towardsaid surface causes said ions to contact said collecting surface.
 3. Anapparatus according to claim 1 wherein said means for directing saidions toward said collecting surface causes said ions to contact saidsurface with sufficient energy to produce surface induced dissociationfragmentation of said ions.
 4. An apparatus according to claim 1 whereinsaid means for directing said ions toward said collecting surface causessaid ions to soft land on said surface.
 5. An apparatus according toclaim 1 wherein said collecting surface comprises a dielectric material.6. An apparatus according to claim 1 wherein said collecting surfacecomprises a piezo material.
 7. An apparatus according to claim 1 whereinsaid collecting surface comprises a self assembled monolayer material.8. An apparatus according to claim 1 wherein said collecting surfacecomprises a conductor material.
 9. An apparatus according to claim 1wherein said collecting surface comprises a semiconductor material. 10.An apparatus according to claim 1 wherein said collecting surfacecomprises multiple layers of conductor and dielectric materials.
 11. Anapparatus according to claim 1 wherein said collecting surface comprisesa MALDI matrix.
 12. An apparatus according to claim 11 wherein said ionsdirected toward said collecting surface are collected on said collectingsurface, said surface collected ions or neutralized molecules areextracted from said surface using a MALDI laser pulse.
 13. An apparatusaccording to claim 1 wherein said collecting surface is heated totemperature above ambient temperature.
 14. An apparatus according toclaim 1 wherein said collecting surface is cooled to a temperature belowambient temperature.
 15. An apparatus according to claim 1 wherein saidcollecting surface is replaceable.
 16. An apparatus according to claim 1wherein said collecting surface comprises a moveable continuous belt.17. An apparatus according to claim 1 wherein said ion source is anatmospheric pressure ion source.
 18. An apparatus according to claim 1wherein said ion source is an Electrospray ion source.
 19. An apparatusaccording to claim 1 wherein said ion source is an Atmospheric PressureChemical Ionization source.
 20. An apparatus according to claim 1wherein said ion source is a Matrix Assisted Laser Desorption Ionizationsource.
 21. An apparatus according to claim 1 wherein said ion sourceproduces ions in vacuum.
 22. An apparatus according to claim 1 whereinsaid ion source is Electron Ionization source.
 23. An apparatusaccording to claim 1 wherein said ion source is a Chemical Ionizationsource.
 24. An apparatus according to claim 1 wherein saidTime-Of-Flight mass analyzer comprises an ion reflector.
 25. Anapparatus according to claim 1, wherein said means for accelerating ionsinto said TOF mass analyzer comprises an electric field applied in saidpulsing region.
 26. An apparatus for analyzing chemical speciescomprising: a mass analyzer comprising a pulsing region and a detector;said mass analyzer further comprising a collecting surface within saidpulsing region for collection of ions on said collecting surface; an ionsource that generates ions from a sample substance away from saidcollecting surface; means for directing said ions toward said collectingsurface; and means for accelerating said ions into said mass analyzer,wherein said collecting surface provides means for collecting ions on ornear said collecting surface.
 27. An apparatus according to claim 26,wherein said means for directing said ions toward said surface causessaid ions to contact said collecting surface.
 28. An apparatus accordingto claim 26, wherein said means for directing said ions toward saidcollecting surface causes ions to contact said surface with sufficientenergy to produce surface induced dissociation fragmentation of saidions.
 29. An apparatus according to claim 26, wherein said means fordirecting said ions toward said collecting surface causes said ions tosoft-land on said surface.
 30. An apparatus according to claim 26,wherein said apparatus comprises means for preventing said ions fromentering said pulsing region.
 31. An apparatus according to claim 26,wherein said collecting surface comprises a dielectric material.
 32. Anapparatus according to claim 26, wherein said collecting surfacecomprises a piezo material.
 33. An apparatus according to claim 26,wherein said collecting surface comprises a self assembled monolayermaterial.
 34. An apparatus according to claim 26, wherein saidcollecting surface comprises a conductor material.
 35. An apparatusaccording to claim 26, wherein said collecting surface comprises asemiconductor material.
 36. An apparatus according to claim 26, whereinsaid collecting surface comprises a multiple layer of conductor anddielectric materials.
 37. An apparatus according to claim 26, whereinsaid collecting surface is heated to a temperature above ambienttemperature.
 38. An apparatus according to claim 26, wherein saidcollecting surface is cooled to a temperature below ambient temperature.39. An apparatus according to claim 26, wherein said surface isreplaceable.
 40. An apparatus according to claim 26, wherein saidsurface is a moveable continuous belt.
 41. An apparatus according toclaim 26, wherein said ion source is an atmospheric pressure ion source.42. An apparatus according to claim 26, wherein said ion source is anElectrospray ion source.
 43. An apparatus according to claim 26, whereinsaid ion source is an Atmospheric Pressure Chemical Ionization source.44. An apparatus according to claim 26, wherein said ion source is aMatrix Assisted Laser Desorption Ionization source.
 45. An apparatusaccording to claim 26, wherein said ion source produces ions in vacuum.46. An apparatus according to claim 26, wherein said ion source isElectron Ionization source.
 47. An apparatus according to claim 26,wherein said ion source is Chemical Ionization source.
 48. An apparatusaccording to claim 26, wherein said mass analyzer is a Time-Of-Flightmass analyzer.
 49. An apparatus according to claim 26, wherein said massanalyzer is a Time-Of-Flight mass analyzer with ion reflector.
 50. Anapparatus according to claim 26, wherein said mass analyzer is a threedimensional ion trap mass analyzer.
 51. An apparatus according to claim26, wherein said mass analyzer is a Fourier Transform mass analyzer.